Immune checkpoint inhibitor therapy-induced autoimmune polyendocrine syndrome type II and Crohn's disease: A case report.

BACKGROUND: The development of immune checkpoint inhibitors (ICIs) has heralded a new era in cancer treatment, enabling the possibility of long-term survival in patients with metastatic disease. Unfortunately, ICIs are increasingly implicated in the development of autoimmune diseases. CASE SUMMARY: We present a man with squamous cell carcinoma of the oropharynx on a combination of teriprizumab, docetaxel, and cisplatin therapy who developed autoimmune polyendocrine syndrome type II (APS-2) including thyroiditis and type 1 diabetes mellitus and Crohn's disease (CD). He developed thirst, abdominal pain, and fatigue after two-week treatment with the protein 1 ligand inhibitor teriprizumab. Biochemistry confirmed APS-2 and thyrotoxicosis. He was commenced on an insulin infusion. However, his abdominal pain persisted. Follow-up surgery confirmed CD and his abdominal pain was relieved by mesalazine. He was continued on insulin and mesalazine therapy. CONCLUSION: Immunotherapy can affect all kinds of organs. When clinical symptoms cannot be explained by a single disease, clinicians should consider the possibility of multisystem damage.

Ghrelin promotes differentiation of human embryonic stem cells into cardiomyocytes.

AIM: Ghrelin is involved in regulating the differentiation of mesoderm-derived precursor cells. The aim of this study was to investigate whether ghrelin modulated the differentiation of human embryonic stem (hES) cells into cardiomyocytes and, if so, whether the effect was mediated by growth hormone secretagogue receptor 1α (GHS-R1α). METHODS: Cardiomyocyte differentiation from hES cells was performed according to an embryoid body (EB)-based protocol. The cumulative percentage of beating EBs was calculated. The expression of cardiac-specific markers including cardiac troponin I (cTnI) and α-myosin heavy chain (α-MHC) was detected using RT-PCR, real-time PCR and Western blot. The dispersed beating EBs were examined using immunofluorescent staining. RESULTS: The percentage of beating EBs and the expression of cTnI were significantly increased after ghrelin (0.1 and 1 nmol/L) added into the differentiation medium. From 6 to 18 d of differentiation, the increased expression of cTnI and α-MHC by ghrelin (1 nmol/L) was time-dependent, and in line with the alteration of the percentages of beating EBs. Furthermore, the dispersed beating EBs were double-positively immunostained with antibodies against cTnI and α-actinin. However, blockage of GHS-R1α with its specific antagonist D-[lys(3)]-GHRP-6 (1 µmol/L) did not alter the effects of ghrelin on cardiomyocyte differentiation. CONCLUSION: Our data show that ghrelin enhances the generation of cardiomyocytes from hES cells, which is not mediated via GHS-R1α.

[Protective effect of calcium dobesilate against early diabetic nephropathy of rat kidney].

The aim of this study is to study the effect of calcium dobesilate on streptozotocin (STZ)-induced early diabetic nephrophathy (DN) in rats. All male Wistar rats were randomly divided into six groups: normal group; DN blank group; calcium dobesilate 75, 150, and 300 mg x kg(-1) groups and perindopril 0.4 mg x kg(-1) group. Blood glucose and the 24 h urinary albumin were measured dynamically during the experiment, after 8 weeks administration, the level of glycosylated hemoglobin (HbA1c) was determined, the expressions of plasminogen activator inhibitor-1 (PAI-1) and matrix metalloprotein-9 (MMP-9) in cortex of kidney were examined with immunohistochemical staining. The endothelin (ET) in plasma and kidney cortex was measured with radioimmunoassay, renal pathomorphism was observed with light and electron microscopes. Calcium dobesilate could decrease the 24 h urinary albumin and ET in plasma and kidney cortex, down-regulate the expression of PAI-1, and up-regulate MMP-9 in kidney. These findings suggested that calcium dobesilate could protect blood vessel endothelium, inhibit kidney fibrous degeneration, ameliorate renal pathological damage, and protect kidney function in many ways.

[Investigation on Fourier transform infrared spectrum of metastatic lymph node in thyroid cancer].

The aim of the study is to explore the possibility of detecting metastatic lymph nodes by FTIR spectra during the surgery of thyroid cancer. The FTIR spectra of 20 metastatic lymph nodes and 69 non-metastatic ones were collected via an ATR (attenuated total reflectance) probe. For each spectrum, 28 variables of 13 bands including peak positions and relative intensities were measured. The variables of metastatic lymph node were compared to those of non-metastatic ones using standard statistic methods. The results indicated that the FTIR spectra of metastatic lymph nodes were significantly different from non-metastatic ones in the bands related to protein, lipid, nucleic acid and carbohydrate. (1) Variations of bands related to protein: The relative intensity ratios of I3 280 /I1 460, I1 640 /I1 460 and I1 546/I1 460 increased significantly (P < 0.05); (2) Variations of bands related to lipid: The relative intensity ratios of I1 743 /I1 460 decreased significantly (P < 0.05). On the contrary, I 400 /I1 460 increased significantly (P < 0.05); (3) The peak positions of 1 165 and 1 120 cm(-1) which were all assigned to carbohydrate shifted toward higher wave number (P < 0.05). The relative intensity ratio of I1 165 /I1 460 decreased significantly (P < 0.05); (4) The peak positions of 1 085 cm(-1) related to nucleic acid shifted to the lower wave number (P < 0.05); (5) Other undetermined bands: The relative intensity ratios of I1 303 /I1 460 and I1 303 /I1 240 increased significantly (P < 0.05). FTIR spectroscopy could be a reliable and practicable method for metastatic lymph nodes diagnosis in the operation of thyroid cancer. It could be applied in detecting metastatic lymph nodes which can not be determined by palpation in surgery.

Dynamic expression of microRNAs during the differentiation of human embryonic stem cells into insulin-producing cells.

Human embryonic stem (hES) cells with the capacity of self-renewal and multilineage differentiation are promising sources for generation of pancreatic islet cells for cell replacement therapy in diabetes. Here we induced hES cells into insulin-producing cells (IPCs) in a stepwise process which recapitulated islet organogenesis by directing cells through the stages resembling definitive endoderm, gut-tube endoderm, pancreatic precursor and cells that expressed pancreatic endocrine hormones. The dynamic expression of microRNAs (miRNAs) during the differentiation was analyzed and was compared with that in the development of human pancreatic islets. We found that the dynamic expression patterns of miR-375 and miR-7 were similar to those seen in the development of human fetal pancreas, whereas the dynamic expression of miR-146a and miR-34a showed specific patterns during the differentiation. Furthermore, the expression of Hnf1ß and Pax6, the predicted target genes of miR-375 and miR-7, was reciprocal to that of miR-375 and miR-7. Over-expression of miR-375 down-regulated the expression of gut-endoderm/pancreatic progenitor specific markers Hnf1ß and Sox9. Therefore, the miRNAs may directly or indirectly regulate the expression of pancreatic islet organogenesis-specific transcription factors to control the differentiation and maturation of pancreatic islet cells.